# Microbial methylglyoxal promotes periodontal inflammation

> **NIH NIH R03** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2022 · $160,084

## Abstract

Project summary
Tannerella forsythia is a leading pathogen implicated in periodontitis, a common chronic
inflammation of the tooth-supporting apparatus (periodontium) that often results in tooth
loss in adults. T. forsythia produces a highly reactive electrophilic compound
methylglyoxal (MGO), which can chemically modify and cross-link biomolecules,
disrupting their structure-function integrity. MGO causes the formation of what are known
as the advanced glycation endproducts (AGEs), which can activate RAGE (receptor of
AGEs) receptor, trigger a perpetuating pro-inflammatory, and pro-adhesive environment
to drive tissue damage. The ability of T. forsythia to produce MGO is due to the presence
of an enzyme, methylglyoxal synthase (MgsA), involved in the synthesis of MGO.
Strikingly, the other two dominant periodontal pathogens implicated in periodontitis,
namely Porphyromonas gingivalis and Treponema denticola, lack any homologs of this
enzyme. It remains to be determined, however, if indeed microbially derived MGO from
T. forsythia contributes to periodontal inflammation and what is the mechanistic basis of
MGO-induced inflammation in the periodontium. In this study we will test the hypothesis
that T. forsythia produced MGO by promoting AGEs is involved in the induction of a
sustained inflammatory response detrimental to the periodontal tissues. We will test our
hypothesis by completion of the following specific aims: 1) Molecular characterization of
T. forsythia MGO modified host and bacterial proteins and 2) Determine the role of MGO
in oral microbial dysbiosis and T. forsythia induced periodontitis. The study will increase
our understanding of the pathogenic mechanisms of T. forsythia by elucidating the role of
MGO as a novel virulent component of the bacterium. Overall, this knowledge might aid
in designing new therapeutic approaches in improving oral and systemic health.

## Key facts

- **NIH application ID:** 10574281
- **Project number:** 1R03DE032392-01
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** Rajendra Prasad Settem
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $160,084
- **Award type:** 1
- **Project period:** 2022-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10574281

## Citation

> US National Institutes of Health, RePORTER application 10574281, Microbial methylglyoxal promotes periodontal inflammation (1R03DE032392-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10574281. Licensed CC0.

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